Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records

Bingyu Zhang; Deepika Thacker; Ting Zhou; Dazheng Zhang; Yuqing Lei; Jiajie Chen; Elizabeth A Chrischilles; Dimitri A Christakis; Soledad Fernandez; Vidu Garg; Susan Kim; Abu S M Mosa; Marion R Sills; Bradley W Taylor; David A Williams; Qiong Wu; Christopher B Forrest; Yong Chen

doi:10.1038/s41467-025-56284-0

Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records

Nat Commun. 2025 Apr 11;16(1):3445. doi: 10.1038/s41467-025-56284-0.

Authors

Bingyu Zhang^{1

2}, Deepika Thacker³, Ting Zhou^{1

4}, Dazheng Zhang^{1

4}, Yuqing Lei^{1

4}, Jiajie Chen^{1

4}, Elizabeth A Chrischilles⁵, Dimitri A Christakis⁶, Soledad Fernandez⁷, Vidu Garg^{8

9}, Susan Kim¹⁰, Abu S M Mosa¹¹, Marion R Sills^{12

13}, Bradley W Taylor¹⁴, David A Williams¹⁵, Qiong Wu^{1

4

16}, Christopher B Forrest^#¹⁷, Yong Chen^#^{18

19

20

21

22

23}

Affiliations

¹ The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA.
² The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
³ Nemours Cardiac Center, Nemours Children's Health System, Wilmington, DE, USA.
⁴ Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
⁵ Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA, USA.
⁶ Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, USA.
⁷ Department of Biomedical Informatics and Center for Biostatistics, Ohio State University, Columbus, OH, USA.
⁸ Heart Center and Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, OH, USA.
⁹ Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
¹⁰ Department of Pediatrics, Division of Pediatric Rheumatology, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
¹¹ Department of Biomedical Informatics, Biostatistics and Medical Epidemiology, University of Missouri School of Medicine, Columbia, MO, USA.
¹² Department of Research, OCHIN, Inc, Portland, OR, USA.
¹³ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
¹⁴ Clinical and Translational Science Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁵ Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
¹⁶ Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁷ Applied Clinical Research Center, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. forrestc@chop.edu.
¹⁸ The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu.
¹⁹ The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu.
²⁰ Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu.
²¹ Leonard Davis Institute of Health Economics, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu.
²² Penn Medicine Center for Evidence-based Practice (CEP), Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu.
²³ Penn Institute for Biomedical Informatics (IBI), Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu.

^# Contributed equally.

Abstract

The risk of cardiovascular outcomes following SARS-CoV-2 infection has been reported in adults, but evidence in children and adolescents is limited. This paper assessed the risk of a multitude of cardiac signs, symptoms, and conditions 28-179 days after infection, with outcomes stratified by the presence of congenital heart defects (CHDs), using electronic health records (EHR) data from 19 children's hospitals and health institutions from the United States within the RECOVER consortium between March 2020 and September 2023. The cohort included 297,920 SARS-CoV-2-positive individuals and 915,402 SARS-CoV-2-negative controls. Every individual had at least a six-month follow-up after cohort entry. Here we show that children and adolescents with prior SARS-CoV-2 infection are at a statistically significant increased risk of various cardiovascular outcomes, including hypertension, ventricular arrhythmias, myocarditis, heart failure, cardiomyopathy, cardiac arrest, thromboembolism, chest pain, and palpitations, compared to uninfected controls. These findings were consistent among patients with and without CHDs. Awareness of the heightened risk of cardiovascular disorders after SARS-CoV-2 infection can lead to timely referrals, diagnostic evaluations, and management to mitigate long-term cardiovascular complications in children and adolescents.

MeSH terms

Adolescent
COVID-19* / complications
COVID-19* / epidemiology
COVID-19* / virology
Cardiovascular Diseases* / epidemiology
Cardiovascular Diseases* / etiology
Child
Child, Preschool
Cohort Studies
Electronic Health Records*
Female
Heart Defects, Congenital / complications
Heart Defects, Congenital / epidemiology
Humans
Infant
Male
Risk Factors
SARS-CoV-2
United States / epidemiology

Abstract

MeSH terms

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